TGF-beta1 as a marker of delayed fracture healing.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
G Zimmerman
Publications and source records attributed to G Zimmerman.
Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields.
In a 2-year bioassay, we exposed Fischer 344 rats to a frequency-modulated (FM) signal (836.55 MHz +/- 12.5 KHz deviation) simulating radiofrequency exposures in the head of users of hand-held mobile phones. We tested for effects on spontaneous tumorigenicity of central nervous system (CNS) tumors in the offspring of pregnant rats and also for modified incidence of primary CNS tumors in rats treated with a single dose of the neurocarcinogen ethylnitrosourea (ENU) in utero. ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months. Pregnant dams (n = 102) were randomly assigned to six groups. Their offspring were treated as cohorts in each of the six groups (n = 90 per group; total, n = 540): Sham ENU/Sham Field, Sham ENU/Field Exposed, ENU/Sham Field, ENU/Field Exposed, ENU/Cage Control, and Sham ENU/Cage Control. Intermittent field exposures began on gestation day 19 and continued until weaning at 21 days, resuming thereafter at 31 days and continuing until experiment termination at 731-734 days. Energy absorption rates (SARs) in the rats' brains were similar to localized peak brain exposures of a phone user (female, 236 g, 1.0 W/kg; male, 450 g, 1.2 W/kg). Of the original 540 rats, 168 died before the termination of the experiment. In these rats, ENU significantly reduced survival from a mean of 708 days in three groups without ENU treatment to 645 days in three groups treated with ENU (P < 0.0005). There were no effects on survival attributable to FM field exposure in either ENU-treated or in sham-treated groups. Spontaneous CNS tumor incidence in control groups was 1.1-4.4% but sharply higher in rats receiving ENU (14.4-22.2%; P < 0.0001). No FM field-mediated changes were observed in number, incidence, or histological type of either spontaneous or ENU-induced brain tumors, nor were gender differences detected in tumor numbers. These negative findings with FM fields contrast with our study using standard digital phone fields pulsed on and off at 50/se, where a trend was noted toward reduced incidence of both spontaneous and ENU-induced CNS tumors (W. R. Adey et al., Radiat. Res., 152: 293-302, 1999). Although consistent but not attaining significance in the experiment overall (spontaneous CNS tumors, P < 0.08 one-tailed; P < 0.16 two-tailed; ENU-induced CNS tumors, P < 0.08 one-tailed, P < 0.16 two-tailed), the trend was significant (P < 0.015 one-tailed, P < 0.03, two-tailed) in rats that received ENU and died prior to experiment termination, with a primary brain tumor as the cause of death. We discuss differences in the signaling structure of digital and FM fields. Certain bioeffects induced by either amplitude-modulated or pulsed radiofrequency fields at athermal levels have not been seen with fields of similar average power but unvarying in intensity (continuous wave or frequency-modulated fields).
Animals↗
Pegaspargase-induced pancreatitis.
BACKGROUND: The purpose of this study is to report the incidence of pancreatitis in patients treated with pegaspargase in our hospital during a 2-year period. PROCEDURE: We identified episodes of pancreatitis related to the intramuscular administration of pegaspargase 2,500 IU/m(2) for the treatment of childhood hematological malignancies during a 2-year period (May 1996-April 1998). Patients were evaluated clinically and by sequential serum amylase and lipase determinations and radiographic examinations. For comparison, episodes of pancreatitis in patients who only received native Escherichia coli L-asparaginase were examined during the same time period. RESULTS: Nine children with acute lymphoblastic leukemia (ALL) of 50 (18%) patients who received pegaspargase were diagnosed to have pancreatitis. All had prior therapy with native L-asparaginase. These children developed symptoms consisting of abdominal pain, nausea, vomiting, and decreased appetite within a median of 15 days from the onset of pegaspargase administration. Six patients became symptomatic after their initial dose. Seven patients developed severe or unacceptable toxicity (grades 3 and 4), measured by increased amylase (>2 times normal) and lipase levels or radiographic evidence of pancreatic inflammation or pseudocyst. One patient also developed hyperammonemia and encephalopathy. In contrast, only one out of 52 (1.9%) ALL patients who received native E. coli L-asparaginase during the same time period developed pancreatitis (P= 0.007). CONCLUSION: Clinicians should be aware of a possible higher incidence of pancreatitis associated with pegaspargase.
Adolescent↗
Patient advocacy groups. A key prescription for dermatology.
In addition to medical care, patient education and support is important to successful treatment of chronic dermatologic diseases. For assistance, dermatologists and patients should turn to patient advocacy groups, which provide educational materials, programs, support groups, and advocacy for patients with chronic skin diseases.
Dermatology↗
Pure sylvian fissure arteriovenous malformations.
OBJECT: Pure sylvian fissure arteriovenous malformations (AVMs) are vascular malformations confined to the sylvian fissure without parenchymal involvement. Because the branches of the middle cerebral artery are arteries of passage and the margins between the AVM and the insula cortex may be ill defined, many surgeons regard pure sylvian fissure AVMs as inoperable. The authors reviewed their surgical experience with eight patients harboring pure sylvian fissure AVMs to determine the incidence of operative morbidity. METHODS: All eight patients experienced seizures, five (63%) had headaches, and three (38%) experienced hemorrhages. Preoperatively, six patients (75%) were normal neurologically and two (25%) had neurological deficits. Five (63%) of eight sylvian fissure AVMs were located in the dominant hemisphere. The size of the nidus ranged from 6 to 27 cm3 (mean 14 cm3). Complete removal of the AVM was documented by postoperative angiography in every case. Seizures were reduced or eliminated and headaches were relieved in all affected patients. Transient neurological deficits, which included aphasia, short-term memory loss, and hemiparesis, occurred in four patients (50%). Within 3 months, all patients were functioning independently with no new neurological deficits. The status of two patients who had had preoperative neurological deficits improved postoperatively. Neuropsychological testing showed no new cognitive deficits. CONCLUSIONS: With appreciation for transient instances of postoperative morbidity, the outcome was excellent in all patients. The authors thus advocate microsurgery as the primary treatment for pure sylvian fissure AVMs.
Adolescent↗
Care for the Caregivers: a program for Canadian military chaplains after serving in NATO and United Nations peacekeeping missions in the 1990s.
The Mental Health Department of the Canadian Forces Support Unit (Ottawa) developed the Care for the Caregivers program to help participants deal with stressful events experienced directly or vicariously from the NATO and United Nations military missions of the 1990s. The program was developed after complaints of postdeployment stress were received from various military care providers. The objectives were to improve the skills of support personnel and to reduce the distress that some caregivers experienced. Thirty-one chaplains who had been exposed to stressful military operations participated in five workshops. These educational 4-day small-group workshops covered topics such as post-traumatic stress disorder, vicarious traumatization, coping techniques, spirituality, self-care, and family issues. An adult education model was chosen to encourage dialogue. Outcomes included reports of professional and personal benefits, requests for additional programs, local education initiatives, and referrals to mental health professionals. Having met its objectives, the program has become a normal concluding part of stressful deployments.
Adaptation, Psychological↗
Evaluation of some criteria used to select patients for brief psychodynamic therapy.
BACKGROUND AND OBJECTIVES: The effectiveness of brief psychotherapy is established, but criteria for the selection of patients remain elusive. This study examines the usefulness of some widely used criteria for the selection of patients for brief psychodynamic therapy (BPT). METHODS: A checklist of 39 criteria often used in a teaching hospital to screen patients for BPT was constructed. Scores derived from a principal components analysis of this checklist provided one set of predictor criteria. A second measure was derived from the consensual agreement of the independent ratings by 3 prominent advocates of BPT. A third predictor was derived from a similar analysis of items from the checklist on which consensual agreement for their relevance was obtained from the independent ratings of 23 BPT teachers in 16 university-affiliated hospitals. Reliable chart-based ratings of improvement in symptoms, increased insight, and improvement in general functioning of a convenience sample of 43 patients treated with BPT in the outpatient clinic of a teaching hospital served as outcome measures. RESULTS: No correlation between any of the derived predictors and any of the measures of outcome was significant after a Bonferroni correction. CONCLUSION: Teachers and clinicians still do not have good criteria for the selection of patients who will benefit from BPT. Exclusion of severe behavior disorders may, however, improve outcome rates by more than 15%.
Humans↗
Two of the usual suspects, platelet-activating factor and its receptor, implicated in acute lung injury.
Explore the source record for details and available documents.
Animals↗
Abdominal compartment syndrome: does intra-cystic pressure reflect actual intra-abdominal pressure? A prospective study in surgical patients.
BACKGROUND: Abdominal compartment syndrome is defined as the adverse physiologic effects of increased intra-abdominal pressure. Prolonged, unrelieved pressure may lead to respiratory compromise, renal impairment, cardiac failure, shock, and death. Abdominal compartment syndrome is diagnosed by measuring intra-cystic pressure as a reflection of intra-abdominal pressure. To examine the validity of the technique, we conducted a prospective study in surgical patients by directly measuring bladder and abdominal pressures simultaneously during laparoscopic cholecystectomy using a previously described technique. RESULTS: In the present model, the bladder had higher baseline pressures than did the abdomen. Measurements across the bladder wall were not identical, but had high positive correlation coefficient when evaluated on an individual basis. Global analysis of the data for all patients showed a weak correlation coefficient. CONCLUSION: In the present study model, intra-cystic pressure did not reflect actual intra-abdominal pressure. In spite of some limitations in the study design, we feel that further research is warranted to identify other possible variables that may play a role in the relationship between the urinary bladder and the abdominal cavity pressures, providing better means for diagnosis of abdominal compartment syndrome.
Journal Article↗
Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.
We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.
Animals↗
Mouse-Torpedo chimeric alpha-subunit used to probe channel-gating determinants on the nicotinic acetylcholine receptor primary sequence.
1. To determine if structural domains are important for nicotinic acetylcholine receptor (nAChr) channel function, six mouse-Torpedo chimeric alpha-subunits were constructed (Fig. 2) and coexpressed with Torpedo californica beta-, gamma-, and delta-subunits in Xenopus laevis oocytes. 2. nAChRs containing a chimeric alpha-subunit were examined by voltage- and patch-clamp methods to determine their functional characteristics. Dose-response curves from voltage-clamped oocytes were used to estimate EC50's and Hill coefficients. Whole-cell currents were normalized against the alpha-bungarotoxin (alpha-BTX) binding sites to obtain normalized responses to acetylcholine (ACh). Open time constants at 4 microM ACh were used to examine single-channel behavior. 3. The EC50 for ACh was modulated by the N-terminal half of the alpha-subunit. When the Torpedo subunit sequence between position 1 and position 268 was replaced by mouse sequence, the EC50 shifted toward the value for the wild-type mouse subunit. Replacement of either the 1-159 or the 160-268 positions of the Torpedo sequence with the mouse sequence lowered the EC50. This suggests that at least two regions play a role in determining the EC50. 4. When the primary sequence (160-268) of the Torpedo alpha-subunit was introduced in the mouse alpha-subunit (T160-268), the expressed chimeric receptor was nonfunctional. The inverse chimera (M160-268) was functional and the open time constant and EC50 were similar to those of mouse but the normalized response was characteristic of Torpedo. 5. The normalized macroscopic response to ACh (300 microM) of the chimera containing the mouse alpha-subunit showed a ninefold increase relative to the Torpedo wild type. Receptors which contain the C terminal of the mouse alpha-subunit also show an increase in the maximum normalized current. Receptors with the alpha-subunit which contain the Torpedo C-terminal sequence have a lower normalized response. 6. The combined results suggest that AChR channel function is modulated by structural determinants within the primary sequence. These structural domains might modulate channel function through specific allosteric interactions. The lack of response of the T160-268 chimera suggests that a critical interaction essential for the coupling of agonist binding and channel gating was disrupted. This result suggests that the interaction of structural domains within the nAChR primary structure are essential for channel function and that these intractions could be very specific within different nAChR species.
Amino Acid Sequence↗
Extremely-low-frequency magnetic fields disrupt rhythmic slow activity in rat hippocampal slices.
Several studies have indicated that weak, extremely-low-frequency (ELF; 1-100 Hz) magnetic fields affect brain electrical activity and memory processes in man and laboratory animals. Our studies sought to determine whether ELF magnetic fields could couple directly with brain tissue and affect neuronal activity in vitro. We used rat hippocampal slices to study field effects on a specific brain activity known as rhythmic slow activity (RSA), or theta rhythm, which occurs in 7-15 s bursts in the hippocampus during memory functions. RSA, which, in vivo, is a cholinergic activity, is induced in hippocampal slices by perfusion of the tissue with carbachol, a stable analog of acetylcholine. We previously demonstrated that the free radical nitric oxide (NO), synthesized in carbachol-treated hippocampal slices, lengthened and destabilized the intervals between successive RSA episodes. Here, we investigate the possibility that sinusoidal ELF magnetic fields could trigger the NO-dependent perturbation of the rate of occurrence of the RSA episodes. Carbachol-treated slices were exposed for 10 min epochs to 1 or 60 Hz magnetic fields with field intensities of 5.6, 56, or 560 microT (rms), or they were sham exposed. All exposures took place in the presence of an ambient DC field of 45 microT, with an angle of -66 degrees from the horizontal plane. Sinusoidal 1 Hz fields at 56 and 560 microT, but not at 5.6 microT, triggered the irreversible destabilization of RSA intervals. Fields at 60 Hz resulted in similar, but not statistically significant, trends. Fields had no effects on RSA when NO synthesis was pharmacologically inhibited. However, field effects could take place when extracellular NO, diffusing from its cell of origin to the extracellular space,was chelated by hemoglobin. These results suggest that ELF magnetic fields exert a strong influence on NO systems in the brain; therefore, they could modulate the functional state of a variety of neuronal ensembles.
Animals↗
Factors related to quality of life and functional status in 50 patients with head and neck cancer.
Quality of life (QOL) and functional status (FS) have become important outcome measures in cancer therapy. Valid and reliable instruments recently have been developed for examining QOL and FS in patients with head and neck (HN) cancer. The present study evaluated the relationships of QOL and FS to physical and psychological variables assumed to affect QOL and FS. Fifty patients were evaluated up to 6 years after HN cancer surgery using one general QOL instrument and three HN-specific instruments. Analysis of variance showed physical variables such as tumor site to be related to HN-specific scores, while psychosocial variables such as marital status were related to general QOL scores (P < or = .05). Several relationships were seen between physical or psychosocial variables and FS or QOL measures; however the relationships were not as strong or direct as expected.
Adult↗
Recurrent urinary conduit bleeding in a patient with portal hypertension: management with a transjugular intrahepatic portosystemic shunt.
OBJECTIVE: To determine if a transjugular intrahepatic portosystemic shunt can control recurrent urinary conduit bleeding in a patient with portal hypertension. METHODS: Following transjugular catheterization of the right hepatic vein, a long curve Colapinto needle was advanced through the liver parenchyma into the portal vein near its bifurcation. After a guide wire exchange, a catheter was advanced into the portal system and venogram was obtained. Following another guide wire exchange, a balloon angioplasty catheter was used to create the shunt by dilating the parenchymal tract between the hepatic and portal veins. A self-expandable stent was used to ensure patency of the shunt. RESULTS: After shunt placement, bleeding from the ileal conduit and stroma decreased significantly. A duplex ultrasound at five-month follow-up demonstrated the shunt to be completely patent. CONCLUSIONS: Based on this limited experience, it appears that the transjugular, intrahepatic, portosystemic shunt is an acceptable method to control massive, recurrent urinary conduit bleeding in patients with portal hypertension.
Aged↗
Computed tomographic findings after acute carbon monoxide poisoning.
Selective necrosis and degeneration of the globus pallidus are characteristic autopsy findings in patients with severe carbon monoxide (CO) poisoning. The objective of this study was to show that computed tomography (CT) may demonstrate these morphological changes in the brain during life, and provide a clue to prognosis. The authors reviewed the medical records of 19 consecutive patients with acute CO poisoning who underwent CT examination during hospitalization. Abnormal CT findings were found in 10 of the 19 patients (53%). The most common abnormal findings were low-density areas in the basal ganglia. These lesions were found in 7 of the 10 cases, and varied from small (limited to the globus pallidus) to large (extending to the internal capsule). Of the 10 patients with abnormal CT scans, 9 survived to hospital discharge but all had some degree of functional neurological impairment. Eighty-nine percent (8 of 9) of the patients with normal CT scans were discharged neurologically intact. Awareness of the potential for basal ganglia lesions in CO poisoning should lead to more accurate CT interpretation and may have significant prognostic implications.
Acute Disease↗
Treatment of mandibular class III periodontal furcation defects. Coronally positioned flaps with and without expanded polytetrafluoroethylene membranes.
Twenty-six mandibular class III furcation defects were treated in 26 subjects using a regenerative therapy that included citric acid root conditioning, placement of freeze-dried decalcified bone allograft and coronally positioned flaps secured by crown-attached sutures. In addition to this therapy, expanded polytetrafluoroethylene (ePTFE) membranes were placed in 14 of the 26 defects. The effect of these therapies was evaluated after 52 to 60 weeks through a series of soft and hard tissue probing measurements including residual furcation classification. For both treatments, mean improvements were observed for furcal probing attachment levels, furcal bone levels, and defect volumes. However, only a few of these through-and-through defects had become closed as judged by a panel of 3 independent examiners. Four defects in each of the 2 treatment groups had changed from Class III to Class I/II or Class II/II evaluated with the soft tissue in place. One defect treated without membrane and 3 defects treated with membranes had changed from Class III to Class II as recorded after reflection of the soft tissues at re-entry. Little difference was observed between defects treated with and without membranes. Further studies with larger sample sizes and longer observation times are needed to fully evaluate these regenerative procedures and their potential for healing Class III furcation defects.
Adult↗
ATP sulfurylase from higher plants: kinetic and structural characterization of the chloroplast and cytosol enzymes from spinach leaf.
Two forms of ATP sulfurylase were purified from spinach leaf. The major (chloroplast) form accounts for 85 to 90% of the total leaf activity (0.03 +/- 0.01 adenosine-5'-phosphosulfate (APS) synthesis units x gram fresh weight-1). Both enzyme forms appear to be tetramers composed of 49- to 50-kDa subunits with the minor (cytosolic) form being slightly larger than the chloroplast form. The specific activities (units x milligram protein-1) of the chloroplast form at pH 8.0, 30 degrees C, were as follows: APS synthesis, 16; molybdolysis, 229; ATP synthesis, 267; selenolysis, 4.1; fluorophosphate activation, 11. Kinetic constants for the physiological reaction were as follows: KmA = 0.046 mM, K(ia) = 0.85 mM, KmB = 0.25 mM, KmQ = 0.37 microM, K(iq) = 64-85 nM, and KmP = 10 microM, where A = MgATP, B = SO4(2-), P = total PPi at 5 mM Mg2+, and Q = APS. The kinetic constants for molybdolysis were similar to those of the APS synthesis reaction. The kinetic constants of the minor (cytosol) form were similar to those of the major form with two exceptions: (a) The molybdolysis activity was 120 units x milligram protein-1, yielding a Vmax (ATP synthesis)/Vmax (molybdolysis) ratio close to 2 (compared to about unity for the chloroplast form) and (b) KmA was greater (0.24 and 0.15 mM for APS synthesis and molybdolysis, respectively). Initial velocity measurements (made over an extended range of MgATP and SO4(2-) concentrations), product inhibition studies (by initial velocity methods and by reaction progress curve analyses), dead end inhibition studies (with monovalent and divalent oxyanions), and kcat/Km comparisons (for SO4(2-) and MoO4(2-) support a random AB-ordered PQ kinetic mechanism in which MgATP and SO4(2-) bind in a highly synergistic manner. Equilibrium binding studies indicated the presence of one APS site per subunit. HPLC elution profiles of chymotryptic and tryptic peptides were essentially the same for both enzyme forms. The N-terminal sequence of residues 5-20 of the cytosol enzyme was identical to residues 1-16 of the chloroplast enzyme.
Adenosine Phosphosulfate↗
Antimicrobial properties of human dentin impregnated with tetracycline HCl or chlorhexidine. An in vitro study.
Substantivity of tetracycline HCl and chlorhexidine digluconate to human root dentin was assessed in vitro. 51 extracted single-rooted teeth, their crowns removed, were assigned to 1 of 4 treatments in groups of 12. A control groups included 3 roots. Each group was divided into 3 subgroups to allow evaluation of drug exposure for 1, 3 or 5 min. The roots were immersed in tetracycline HCl (10 or 50 mg/ml) or chlorhexidine digluconate (0.12 or 0.2%) solutions following root planning. Control roots were immersed in sterile saline (0.9%). Following drug immersion, the roots were transferred to tubes containing 2 ml tris buffered saline. The tubes were incubated at room temperature for 22 days. Desorption media were replaced at 24-h intervals. Removed media were examined for antimicrobial activity using a microtiter assay in which bacterial growth was evaluated by optical density readings. Roots immersed in tetracycline HCl 50 mg/ml released antimicrobial activity to successive desorption media for 14 days. Tetracycline HCl 10 mg/ml activity lasted 4 days. Roots subjected to chlorhexidine digluconate released antimicrobial activity for 24 h only. Within each treatment, there were no differences between the 3 exposure intervals of 1, 3 or 5 min. Our findings suggest usage of the periodontally exposed instrumented root as a depot for sustained release of tetracycline HCl, but not chlorhexidine digluconate, to the subgingival environment. The substantiveness of tetracycline HCl seems related to drug concentration rather than the exposure interval. Clinical trials are needed to confirm the clinical significance of these in vitro observations.
Adsorption↗